We have isolated human monoclonal autoantibodies that each react with antigens in a variety of organs and are termed multiple organ reactive (MOR) antibodies. Using MOR immunoaffinity columns we have attempted to isolate and characterize the autoantigens in human tissues. We are attempting to determine whether diagnostically or prognostically useful screening procedures can be devised for the antigens and/or anti-idiotypic antibodies that react with MOR antibodies. We have found that lymphocytes capable of producing MOR antibodies are a normal part of the B cell repertoire. Using both standard fusion techniques and EBV transformation, cell lines secreting monoclonal MOR autoantibodies were obtained using lymphocytes from normal individuals. Thus, lymphocytes capable of making autoantibodies are present, but silent, under normal conditions but can at times be triggered by environmental factors to produce autoantibodies.